Efforts to reduce infarct size have been confined almost exclusively to myocardial necrosis following coronary occlusion. While this problem is undoubtedly important, we have chosen to study necrosis in a different context. Acute myocardial infarction in humans usually occurs remote from the hospital and the time delay before therapy can be instituted is a major handicap. Myocardial infarction during cardiac surgery is an important problem and, ideally, therapy could be applied prophylactically. Although the aim of aortocoronary bypass surgery is to increase the blood flow to ischemic myocardium, too often any benefits are diminished by postoperative myocardial infarction. In this situation, in contrast to spontaneous myocardial infarction, the time and place of the event are known in advance. We suggest two mechanisms are possible. First, the native circulation or the graft could occlude during or immediately after the operation. Second cardiac operations demand a period of ischemia followed by reflow. We wish to determine if this second mechanism - reperfusion necrosis - occurs in humans. Our previous work extends earlier experimental observations and shows that the evolution of epicardial electrocardiographic changes not only permits recognition of necrosis but the time sequence points to the mechanism responsible. Further, we and others have shown that in dog models reperfusion necrosis can be prevented or diminished by pharmacologic therapy. Therefore, this proposal has two objectives: first, to examine the effect of drugs on the extent of reperfusion necrosis in a dog model we have developed, and second, to examine the perioperative ECG changes in patients undergoing bypass or valvular surgery to determine the importance of reperfusion necrosis in postoperative myocardial infarction.